Prostate cancer is the second leading cause of cancer-related death in men in the United States. Studies indicate that 30-45% of patients with clinically localized disease are found with Stage T3. These patients have extra-capsular extension, where prostate cancer cells have extended into or beyond the outer lining of the prostate gland. In these patients, cancer may relapse and metastasize after local therapy.
In fact, a large percentage of androgen-independent prostatic carcinomas metastasize to bone. These metastases are difficult to treat and contribute to increased morbidity and mortality, with a median survival of approximately a year after diagnosis.
Despite the effectiveness of hormone therapy, most patients with metastatic disease eventually progress to an androgen-independent state at which time the disease is incurable with a median survival rate of 1 year. Overall, the 5-year survival rate for metastatic prostate cancer is only 34%. New diagnostic, prognostic, and therapeutic approaches are clearly needed for the treatment of advanced and metastatic prostate cancer.
One approach is antibody therapy. However, the antibodies currently available for detection and treatment of prostate cancers are limited. The MAb 7E11-05.3, which binds to Prostate-Specific Membrane Antigen (PSMA), has been developed for clinical trials. The ProstaScint® scan (Cytogen, Princeton, N.J.), based on Indium-111 labeled 7E11-05.3, appears superior to the conventional imaging methods for soft-tissue disease, but has limitations because it binds to the intracellular domain on PSMA. In addition, PMSA is not expressed in certain advanced, androgen-independent tumor cells such as PC3 and Du145, and therefore this antibody is not useful for imaging bone metastases. Recent studies show that the anti-prostate stem cell antigen (PSCA) MAb1G8 can inhibit tumor growth of androgen-dependent tumor xenografts. However, anti-PSCA MAbs are ineffective against androgen-independent PC3 tumors, which do not express PSCA. An analysis of prostate cancer tissue sections demonstrated that PSCA is absent in about 20% of specimens. Therefore, defining new prostate specific markers is important in order to improve the diagnosis and treatment of advanced androgen-independent prostate cancer.